iStopMM: Screening for MGUS Enables Earlier Detection and Intervention

Take-aways:

• In the iStopMM study, population-based screening for MGUS identified a significantly higher number of patients with active malignancy or smoldering disease.
• After a median follow-up of 3 years, 194 patients with MGUS had been diagnosed with any lymphoproliferative disorder.
• Investigators advised against systematic MGUS screening in healthy individuals until the final iStopMM results on survival and quality-of-life data are available.

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In the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) study, researchers explored whether population-based screening for monoclonal gammopathy of undetermined significance (MGUS) could increase the frequency of patients with multiple myeloma being diagnosed in the precursor state. According to findings from the study presented at the 2021 American Society of Hematology Annual Meeting, systematic screening identified a significantly higher number of patients with active malignancy or smoldering disease, suggesting that early detection and intervention are achievable.

Even though individuals who develop multiple myeloma during screening for the precursor state MGUS have better overall survival and fewer complications than patients with multiple myeloma diagnosed without knowledge of MGUS, “less than 5% of all multiple myeloma patients are diagnosed during their precursor state,” the study authors wrote.
iStopMM researchers invited all Icelandic residents born before 1976 to participate in MGUS screening. A total of 75,422 participants provided a serum sample for analysis. Of those, 3,725 newly diagnosed individuals with MGUS were identified and 3,487 were enrolled in the follow-up randomized controlled portion of the trial.

In the randomized portion, patients with MGUS were either not contacted (arm 1), followed based on current guidelines (arm 2), or followed with a more intensive diagnostic and monitoring strategy (arm 3). Individuals who progressed to multiple myeloma were offered early treatment, and all participants routinely submitted quality of life and mental health questionnaires.

Researchers reported that MGUS prevalence was higher in males at 5.9% versus 4.1% (P < .0001). Prevalence was also correlated with age, with 2.3%, 6.2%, and 12.9% of patients diagnosed in respective age groups of 40-59, 60-79, and 80-103 years.

After a median follow-up of 3 years, 194 patients had been diagnosed with any lymphoproliferative disorder—specifically, 9 patients in arm 1, 92 in arm 2, and 133 in arm 3 (P < .001). The difference between arms was statistically significant for all lymphoproliferative disorders combined, and for smoldering Waldenström macroglobulinemia, smoldering myeloma, and multiple myeloma diagnoses.

The initial analysis of the iStopMM data suggest that “early detection and intervention is achievable,” according to the investigators. However, though they called the findings encouraging, they advised against systematic MGUS screening in healthy individuals until the iStopMM study concludes and final results including survival and quality-of-life data are available.

Disclosures: This research was supported by the University of Iceland. The study authors reported no relevant conflicts of interest.

Reference

Kristinsson SY, Rögnvaldsson S, Thorsteinsdottir S, et al. Screening for monoclonal gammopathy of undetermined significance: a population-based randomized clinical trial. First results from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study. Abstract #156. Presented at the 2021 American Society of Hematology Annual Meeting, December 11, 2021.